This invention relates generally to monoclonal antibodies, and more particularly, relates to a murine monoclonal antibody which specifically binds to HIV-2 and does not significantly bind to HIV-1, uses for the monoclonal antibody, and kits which contain the monoclonal antibody.
Present epidemiological data suggest that the Acquired Immunodeficiency Syndrome (AIDS) is caused by at least two types of human immunodeficiency viruses, collectively designated as HIV. Human immunodeficiency virus type 1 (HIV-1) has been isolated from patients with AIDS and AIDS-related complex (ARC), and from healthy persons at high risk for AIDS. See, for example, F. Barre-Sinoussi et al., Isolation of T-Lymphotropic Retrovirus From a Patient At Risk For Acquired Immune Deficiency Syndrome (AIDS), Science 220:868-871 (1983); M. Popovic et al., Detection, Isolation and Continuous Production Of Cytopathic Retroviruses (HTLV-III) From Patients With AIDS are Pre-AIDS, Science 224:497-500 (1984); and R. C. Gallo et al., Frequent Detection and Isolation Of Cytopathic Retroviruses (HTLV-III) From Patients With AIDS and At Risk For AIDS, Science 224:500-503 (1984).
HIV-1 reportedly is transmitted by sexual contact, exposure to blood or certain blood products, or from an infected mother to her fetus or child. P. Piot et al., AIDS: An International Perspective, Science 239:573-579 (1988). Also, the incidence of HIV-1 antibodies is high in AIDS and ARC patients and persons at risk. M. G. Sarngadharan et al., Antibodies Reactive With Human T-Lymphotrophic Retroviruses (HTLV-III) In The Serum of Patients With AIDS, Science 224:506-508 (1984). This virus can be isolated from nearly 90% of all seropositive individuals. D. Gallo et al., Comparative Studies On Use Of Fresh and Frozen Peripheral Blood Lymphocyte Specimens For Isolation Of Human Immunodeficiency Virus and Effects Of Cell Lysis On Isolation Efficiency, J. Clin. Microbiology 25:1291-1294 (1987).
A second HIV virus, designated as Human Immunodeficiency Virus Type 2 (HIV-2), was isolated from patients with AIDS in West Africa in 1986. F. Clavel et al., Isolation Of a New Human Retrovirus From West African Patients With AIDS, Science 233:343-346 (1996). HIV-2 infections now have been identified in humans outside of the initial endemic area, and have been reported in Europeans who have lived in West Africa or those who have had sexual relations with individuals from this region, homosexuals with sexual partners from the endemic area, and others. See, for example, A. G. Saimot et al., HIV-2/LAV-2 In Portuguese Man With AIDS Who Had Served In Angola In 1968-74, Lancet i:686 (1987); M. A. Rey et al., HIV-1 and HIV-2 Double Infection In French Homosexual Male With AIDS-Related Complex, Lancet i:388-389 (1987); A. Werner et al., HIV-2, Lancet i:868-869 (1987); G. Brucker et al., HIV-2 infection In Two Homosexual Men In France, Lancet i:223 (1987); K. Marquart et al., HIV-2 in West Germany, AIDS 2:141 (1988); CDC, AIDS due to HIV-2 infection, MMWR 37:33-35 (1987); Anon., HIV-2 Detected In UK, Nature 332:295 (1988).
Retrospectively-diagnosed cases of AIDS due to HIV-2 infection, acquired in the late 1960's, have been reported in France and the United Kingdom, and the first examples of transfusion associated HIV-2 infection recently have been documented. N. Burin des Roziers, Infection Par Le Virus HIV-2 Avec Longue Period D'incubation, Presse Med 16:1981 (1987); A. Bryceson et al., HIV-2 Associated AIDS In The 1970's, Lancet ii:221 (1988); and A. M. Courouce et al., A Prospective Study of HIV-2 Prevalence In France, AIDS 2:261-265 (1988).
The differentiation of HIV-2 from HIV-1 is based on the following factors: (1) HIV-1 DNA probes constructed with the entire genome fail to hybridize with HIV-2 RNA under medium or high stringency conditions; (2) there is less than 60% amino acid identity (HOMOLOGY) for the gag and pol gene products, and only 37% for env encoded proteins between the two viruses; and (3) HIV-1 antibody containing sera have no neutralizing effect on HIV-2 isolates, contrasting with the cross-neutralization activity of HIV-2 antisera on HIV-1 strains. F. Clavel, HIV-2, The West African AIDS Virus, AIDS 1:135-140 (1987); R. A. Weiss et al., HIV-2 Antisera Cross-Neutralize HIV-1, AIDS 2:95-100 (1988). Serologic studies indicate that while HIV-1 and HIV-2 share multiple common epitopes in their core antigens, the envelope glycoproteins of these two viruses are much less cross-reactive. F. Clavel, supra. This limited cross-reactivity of the envelope antigens is believed to explain why currently available serologic assays for HIV-1 may fail to react with certain sera from individuals with antibody to HIV-2. F. Denis et al., Comparison Of 10 Enzyme Immunoassays For Detection Of Antibody To HumanImmunodeficiency Virus Type 2 In West African sera, J. Clin. Micro 26:1000-1004 (1988). Recently issued U.S. Pat. No. 5,055,391 maps the HIV-2 genome and provides assays to detect the virus.
Tests developed for detection of HIV-1, HIV-2, or both, thus must contain reagents which are useful for determining the specific presence of either or both of the viruses in a test sample. The need therefore exists for reagents, such as monoclonal antibodies, capable of reacting only with HIV-2 from human sources, which antibody does not cross-react with HIV-1 antigenic determinants.